{"title":"Correction to: Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy.","authors":"","doi":"10.1093/jmcb/mjae032","DOIUrl":"10.1093/jmcb/mjae032","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong
{"title":"ATP promotes protein coacervation through conformational compaction.","authors":"Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong","doi":"10.1093/jmcb/mjae038","DOIUrl":"10.1093/jmcb/mjae038","url":null,"abstract":"<p><p>Adenosine triphosphate (ATP) has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered Arg-Gly/Arg-Gly-Gly (RG/RGG) rich motif from the HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that, at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs and accounts for the distinct phase separation behaviors of the charge-rich RGG motif and other low-complexity IDPs.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypoxia signaling in the adipose tissue.","authors":"Phu M Huynh, Fenfen Wang, Yu A An","doi":"10.1093/jmcb/mjae039","DOIUrl":"10.1093/jmcb/mjae039","url":null,"abstract":"<p><p>Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in humans and rodent models with obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues behave in response to hypoxia. Then, the differential roles of adipose HIF-1α and HIF-2α in adipose tissue biology and obesity pathology are highlighted. Finally, the review emphasizes the importance of modulating adipose hypoxia as a therapeutic avenue to assist adipose tissues in functionally adapting to hypoxic conditions, ultimately promoting adipose health and improving outcomes due to obesity.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A long noncoding RNA with enhancer-like function in pig zygotic genome activation.","authors":"Renyue Wei, Yanbin Yue, Yinhuan Wu, Chenyuan Zhang, Junxue Jin, Zhonghua Liu, Jiaqiang Wang","doi":"10.1093/jmcb/mjae061","DOIUrl":"https://doi.org/10.1093/jmcb/mjae061","url":null,"abstract":"<p><p>The zygotic genome activation (ZGA) is crucial for the development of pre-implantation embryos. Long noncoding RNAs (lncRNAs) play significant roles in many biological processes, but the study on their role in the early embryonic development of pigs is limited. In this study, we identify lncFKBPL as an enhancer-type lncRNA essential for pig embryo development. LncFKBPL is expressed from the 4-cell stage to the morula stage in pig embryos, and interference with lncFKBPL leads to a developmental arrest at the 8-cell stage. Mechanistic investigations uncover that lncFKBPL is able to bind to MED8, thereby mediating enhancer activity and regulating FKBPL expression. Additionally, FKBPL interacts with the molecular chaperone protein HSP90AA1, stabilizing CDK9 and boosting its protein-level expression. Elevated CDK9 levels enhance Pol II phosphorylation, facilitating ZGA. Our findings illuminate the role of lncFKBPL as an enhancer lncRNA in pig ZGA regulation and early embryo development, providing a foundation for further exploration in this area.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca Brooks, Xianhui Wei, Mang Leng Lei, Francisca Cisterna Cid, James A Roper, Rosalind C Williamson, Mark D Bass
{"title":"Inhibition of EphA2 by syndecan-4 in wounded skin regulates clustering of fibroblasts.","authors":"Rebecca Brooks, Xianhui Wei, Mang Leng Lei, Francisca Cisterna Cid, James A Roper, Rosalind C Williamson, Mark D Bass","doi":"10.1093/jmcb/mjae054","DOIUrl":"https://doi.org/10.1093/jmcb/mjae054","url":null,"abstract":"<p><p>Upon injury, fibroblasts in the surrounding tissue become activated, migrating into the wound in a controlled manner. Once they arrive, they contract the wound and remodel the stroma. While certain cell surface receptors promote fibroblast migration, others cause repulsion between fibroblasts upon contact, seemingly opposing their clustering within the wound bed. Eph receptor-ephrin interactions on colliding cells trigger this repulsion, but how fibroblasts transition to clustering behaviour during healing remains unclear. Syndecan-4 modulates transmembrane receptors involved in wound healing, including receptors for the extracellular matrix and growth factors. As a result, Sdc4-/- mice experience delayed healing due to impaired fibroblast recruitment. In this study, we report that syndecan-4 also regulates fibroblast repulsion during wound healing. We discover that syndecan-4 inhibits the expression and signalling of EphA2 by activating PKCα. Changes in syndecan-4 expression, such as those observed during wound healing, alter fibroblast behaviour from repulsion to adhesion upon cell collision by modulating EphA2 levels. Moreover, we find that EphA2 expression is suppressed in wound bed fibroblasts in a syndecan-4-dependent manner, explaining how fibroblast clustering is achieved during wound healing.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding
{"title":"Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.","authors":"Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding","doi":"10.1093/jmcb/mjae030","DOIUrl":"10.1093/jmcb/mjae030","url":null,"abstract":"<p><p>Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sm Faysal Bellah, Fengrui Yang, Fangyuan Xiong, Zhen Dou, Xuebiao Yao, Xing Liu
{"title":"ZW10: an emerging orchestrator of organelle dynamics during the cell division cycle.","authors":"Sm Faysal Bellah, Fengrui Yang, Fangyuan Xiong, Zhen Dou, Xuebiao Yao, Xing Liu","doi":"10.1093/jmcb/mjae026","DOIUrl":"10.1093/jmcb/mjae026","url":null,"abstract":"<p><p>Zeste white 10 (ZW10) was first identified as a centromere/kinetochore protein encoded by the ZW10 gene in Drosophila. ZW10 guides the spindle assembly checkpoint signaling during mitotic chromosome segregation in metazoans. Recent studies have shown that ZW10 is also involved in membrane-bound organelle interactions during interphase and plays a vital role in membrane transport between the endoplasmic reticulum and Golgi apparatus. Despite these findings, the precise molecular mechanisms by which ZW10 regulates interactions between membrane-bound organelles in interphase and the assembly of membraneless organelle kinetochore in mitosis remain elusive. Here, we highlight how ZW10 forms context-dependent protein complexes during the cell cycle. These complexes are essential for mediating membrane trafficking in interphase and ensuring the accurate segregation of chromosomes in mitosis.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sterile activation of RNA-sensing pathways in autoimmunity.","authors":"Jiaxin Li, Junyan Zhu, Hui Yang, Fajian Hou","doi":"10.1093/jmcb/mjae029","DOIUrl":"10.1093/jmcb/mjae029","url":null,"abstract":"<p><p>RNA-sensing pathways play a pivotal role in host defense against pathogenic infections to maintain cellular homeostasis. However, in the absence of infection, certain endogenous RNAs can serve as the activators of RNA-sensing pathways as well. The inappropriate activation of RNA-sensing pathways by self-ligands leads to systemic inflammation and autoimmune diseases. In this review, we summarize current findings on the sterile activation of RNA sensors, as well as its implications in autoimmunity, inflammatory diseases, and therapeutics.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PHLDA2 is critical for p53-mediated ferroptosis and tumor suppression.","authors":"Xin Yang, Wei Gu","doi":"10.1093/jmcb/mjae033","DOIUrl":"10.1093/jmcb/mjae033","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}